ARHGAP9 knockdown promotes lung adenocarcinoma metastasis by activating Wnt/β-catenin signaling pathway via suppressing DKK2

被引：6
|
作者：
Song, Wenping [1 ,2 ,3 ,4 ]
Wu, Xuan [5 ]
Cheng, Cheng [2 ,6 ]
Li, Ding [1 ,2 ]
Chen, Jinhua [1 ,2 ]
Zhang, Wenzhou [1 ,2 ,7 ,8 ]
机构：
[1] Zhengzhou Univ, Affiliated Canc Hosp, Dept Pharm, Zhengzhou 450008, Peoples R China
[2] Henan Canc Hosp, Zhengzhou 450008, Peoples R China
[3] Henan Canc Hosp, Henan Engn Res Ctr Tumor Precis Med & Comprehens E, Zhengzhou 450008, Peoples R China
[4] Henan Canc Hosp, Henan Prov Key Lab Anticanc Drug Res, Zhengzhou 450008, Peoples R China
[5] Zhengzhou Univ, Peoples Hosp, Dept Resp & Crit Care Med, Zhengzhou 450003, Peoples R China
[6] Zhengzhou Univ, Affiliated Canc Hosp, Dept Hematol, Zhengzhou 450008, Peoples R China
[7] Zhengzhou Univ, Affiliated Canc Hosp, Dept Pharm, 127 Dongming Rd, Zhengzhou 450008, Peoples R China
[8] Henan Canc Hosp, 127 Dongming Rd, Zhengzhou 450008, Peoples R China
来源：
GENOMICS | 2023年 / 115卷 / 05期
基金：
中国国家自然科学基金;
关键词：
ARHGAP9; DKK2; Wnt/beta-catenin signaling pathway; Lung adenocarcinoma; Metastasis; PROTEIN; 9; ARHGAP9; CANCER; GENE; EXPRESSION; NSCLC;
D O I：
10.1016/j.ygeno.2023.110684
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
This study aims to elucidate the effect of ARHGAP9 on lung adenocarcinoma (LUAD) metastasis, and preliminarily explore its molecular mechanism. As a result, we found that ARHGAP9 was downregulated and correlated with poor prognosis of LUAD. ARHGAP9 knockdown promoted LUAD cell proliferation, migration and invasion, inhibited cell apoptosis and reduced G0G1 cell cycle arrest, in contrast to the results of ARHGAP9 overexpression. Further RNA sequencing analysis demonstrated that ARHGAP9 knockdown in H1299 cells significantly reduced DKK2 (dickkopf related protein 2) expression. Silencing ARHGAP9 in H1299 cells while overexpressing DKK2, DKK2 reversed the promoted effects of ARHGAP9 knockdown on LUAD cell proliferation, migration and invasion. Meanwhile, the activity of Wnt/beta-catenin signaling pathway was also reduced. Taken together, these data indicated that ARHGAP9 knockdown promoted LUAD metastasis by activating Wnt/beta-catenin signaling pathway via suppressing DKK2. This may provide a new strategy for LUAD treatment.
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页数：11
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